Transporting CRT Medicines in 2019: Part 1
We don’t have to tell you that effective temperature management is critical for ensuring the safety and effectiveness of all types of drugs, even those that may not classify as “cold chain” products such “ambient” or “room temperature” medicines.
Not too long ago, “ambient,” “room temperature” and even “controlled room temperature” (CRT) were considered synonymous and, as they were considered more or less resilient again temperature excursions, were provided little to no thermal protection across the supply chain. However, this is beginning to change. Increased regulatory focus, an improved understanding of how inappropriate storage conditions impact product integrity and the increased volume of temperature sensitive CRT biosimilars/biologics have pushed manufacturers to pay just as much attention to room temperature products as they do traditional cold chain drugs.
This being said, transporting room temperature drugs is not without its challenges. Though it may sound counter-intuitive, safeguarding room products from temperature excursions can actually be more expensive and difficult than protecting their cooler counterparts. From reasons ranging from costs to simple effectiveness, one simply just can’t apply the same solutions and methodologies to ambient products as they do those that require refrigeration.
With this in mind, below we’ve outlined the key challenges and solutions associated with protecting CRT and ambient drugs across the supply chain.
Defining Cold Chain Drugs
Though packaging and storage requirements for frozen and refrigerated drugs have pretty much always been clearly defined (between -10°C to -25°C and +8°C to +15°C, respectively), requirements for “ambient” or “room temperature” drugs are notably more ambiguous. Though some regulatory entities offer some guidance on CRT labeling, the definition of CRT is often entirely dependent on the product being shipped and the length of time it is being shipped for. To complicate the matter, enforcement of these standards are quite inconsistent; while some customs inspectors or health authorities are rigorous about CRT adherence, others are less so.
Definition Cheat Sheet
Below is a breakdown of global regulatory definitions and guidance for ambient drugs. In summary though, terms like "ambient", "room temperature" and "cold chain" should be avoided as the only labelling for storage or transport boxes and containers because they are not always clear and might have different meanings in other parts of the world. Storage conditions should always be explicitly specified in terms of a defined temperature range (e.g., 15°C -25°C or +2°C to +8°C). Particular attention should also be given to avoiding freezing of liquids and semi-solids.
EMA Guidelines on Declaration of Storage Conditions
*definitions sourced from What are the regulatory Definitions for "Ambient", "Room Temperature" and "Cold Chain"? https://www.gmp-compliance.org/gmp-news/what-are-the-regulatory-definitions-for-ambient-room-temperature-and-cold-chain
Know Your Product
Tighten up the data and procedures for determining the stability budget of pharma products to ensure accuracy. Temperature ranges permitted during pharmaceutical product distribution, as well as the labeled storage conditions, are inseparably linked to stability data for each product so “obtaining a clear understanding of the product’s true storage and shipping temperature range is paramount to the stability of that product,” Steve Winyard, Portfolio Manager – Life Sciences at Inmark, told Pharma IQ in 2018. “If a product is being shipped internationally by air transport over two or more days, the packaging requirements would be quite different than if it were shipped domestically using a same or next day delivery service.”
In an article published in WorldPharma, Russell Brierley, Lupin’s Director of Clinical Supplies, advises companies to create excursion profile with their quality group that pre-defines several levels of excursion to allow timely dispensation of any shipments that have temperature excursions:
- Level 1: No temperature excursion, the drug is maintained at its labelled storage condition
- Level 2: The acceptable temperature excursions that do not need any follow-up investigation
- Level 3: The temperature excursions that might consider some quality input or investigation
- Level 4: The temperature excursions where products should be rejected
Know Your Trade Lane
Understanding the likely ambient thermal profile of transit lanes as well as any potential factors (such as hand-offs or check points) that could delay the shipment or result in temp excursions is critical for effectively determining thermal protection and packaging requirements for your product. Where is your product going? Take a look at the full end-to-end journey and, at each touchpoint, evaluate local temperatures, taking into account annual and seasonal average minimum and maximum extreme temperatures, as well as the potential package exposure time associated with that touchpoint.
According to Geoffrey Glauser, Senior Consultant, Conceptual Mindworks Inc., at a minimum, your Lane Characterization process should include:
- Name and address of the sending site
- Name and address of the receiving site
- Quantity of material being shipped
- Product name and labeled storage conditions
- All transport service providers, including trucking companies, airlines, and ocean transport services
- Identification of the touchpoints within the lane
- Identification of all product handoffs
- Annual average minimum and maximum temperature extremes at the sending and receiving sites as well as at all touchpoints within the lane
- Duration of transport between each touchpoint
Invest In Technology
Leading-edge companies are leveraging electronic monitoring and reporting equipment, ranging from throwaway sensors to elaborate global communications networks, to track shipments by geography and by environmental conditions. As a result, logistics providers are now capable of providing near-real-time monitoring of shipment temperatures, from the warehouse to the loading docks of pharmacies and hospitals. The data collected through these sensors can also help develop improved predictive models for future shipments. In fact, according to our 2018 Industry Survey, over 75% of our respondents were looking to invest in temperature monitoring devices in the near future.